Among putative neuroprotection strategies, hypothermia has long been recognized as the most potent. Recent insights in understanding ischemia and reperfusion suggest that hypothermia may be an ideal modality for extending the stroke therapy time window. Although difficulties cooling patients limited testing of this potentially effective therapy, recent developments in technology allow us to mount a Phase 1 clinical trial of intravascular cooling for patients presenting beyond 3 hours. The purpose of this study is to confirm the performance of an endovascular cooling device and to establish the parameters for a larger clinical study, such as sample size and indices of measurement. Preliminary effectiveness of hypothermia treatment in combination with thrombolysis for stroke will also be evaluated in this limited patient population. To do this, we will address 2 specific aims: 1) Characterize the safety profile of hypothermia in stroke patients who initiate cooling between 3 and 6 hours after stroke. Substantial pre-clinical data supports the hypothesis that the window for effective hypothermia may be longer that 3 hours. We will establish safety of the cooling device, and collect outcome data to be used for estimating sample size in larger, Phase 2 trials. 2) Establish the safety of thrombolysis and hypothermia used together between 3 to 6 hours after stroke onset. Thrombolysis trials failed to demonstrate benefit to patients treated later that 3 hours following stroke onset. In each trial, however, there was a trend toward benefit, and meta-analyses suggest that there is a positive, but small effect in later treated patients. We hypothesize that hypothermia, combined with thrombolysis, may prove effective in such patients. We will establish the safety of invasive, endovascular-cooling catheter in combination with thrombolysis. We will collect safety and outcomes data to aid in the design of larger, controlled Phase 2 trial.